This application proposes a four-year renewal of our study to examine the relationship between alcoholism and anxiety disorders and assess the possible mechanisms for this association by applying a family study design. In our original application, we proposed to study two transmissible forms of alcoholism: a pure form that was not associated with any major psychiatric disorder, and a form that was etiologically related to anxiety disorders. The preliminary findings confirm our original hypothesis regarding two transmissible forms of alcoholism. Alcoholism with anxiety can be distinguished from "pure" alcoholism based on patterns of familial aggregation of disorders in adult relatives and, among their offspring, on patterns of psychiatric diagnoses, indicators of brain function (including neuropsychologic testing, event-related potentials and neurologic signs), and on measures of social and behavioral adjustment. In this application, we propose to: (1) increase the samples of alcoholic probands with and without anxiety disorders and their relatives in order to enhance the power of the analyses of familial transmission and comorbidity and enable multivariate analyses that incorporate the effects of gender, clinical severity and tertiary diagnosis in the probands; (2) conduct statistical analyses of the data by comparing the relatives of the alcoholic probands with those of probands with pure anxiety disorder and with relatives of normals. Data collection on the two comparison groups is currently being completed for a separate project. The proposed study is distinguished from earlier family studies of alcoholism because it (a) focuses on the comorbidity of alcoholism and anxiety disorders; (b) proposes to investigate mechanisms for comorbidity through the analysis of patterns of co-segregation of alcoholism and anxiety in families; (c) proposes to evaluate the presence of ascertainment bias among treated alcoholics by selecting probands from both treatment centers and the community. Finding from this study may have important implications for gaining understanding of the specific factors involved in the familial aggregation of alcoholism, and for prevention and intervention of this widespread and disabling disorder.